We have investigated the mechanisms of oncogenes regulation in human malignancies. A large body of evidence has implicated the c-myc oncogene in normal cell growth and differentiation as well as in the development of a wide range of human cancers. This project is designed to study both the mechanisms of transcriptional regulation of the c-myc gene and to examine functional properties of the c-myc protein product. The four major projects are the following: A) Transcriptional regulation of the c-myc oncogene in normal and neoplastic cells. B) Triplex-helix formation with the positive cis-acting DNA sequence to inhibit expression of the c-myc gene. C) Effect of differentiating agents on the function of transcription factors and their role in the regulation of the c-myc gene. D) Search for the function of the c-myc proteins.